Development of complement therapeutics for inhibition of immune-mediated red cell destruction.

A major objective of my National Blood Foundation (NBF)-funded proposal was to produce recombinant soluble forms of a complement regulatory protein called complement receptor 1 (CR1) that carries the Knops blood group system antigens to perform antibody neutralization studies. By generating these recombinant proteins, we were able to inhibit several Knops antibodies in patient serum samples, thereby demonstrating their usefulness for clinical use. Interestingly, the recombinant CR1 proteins generated through NBF funding were also found to strongly reduce complement-mediated red cell destruction in a mouse hemolytic transfusion model. In this review, I will outline our NBF-funded studies, give an overview of recent advances from our group and others in the development of complement therapeutics, and highlight their potential use in the transfusion medicine setting.